Structure-Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent

  • ACS Med Chem Lett. 2017 Feb 3;8(3):344-349. doi: 10.1021/acsmedchemlett.7b00008.
Yanke Liang  1 ,  Melissanne de Wispelaere  2 ,  Margot Carocci  2 ,  Qingsong Liu  1 ,  Jinhua Wang  1 ,  Priscilla L Yang  2 ,  Nathanael S Gray  1
Affiliations
  • 1. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States; Departments of Biological Chemistry & Molecular Pharmacology and Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, United States.
  • 2. Departments of Biological Chemistry & Molecular Pharmacology and Microbiology and Immunobiology, Harvard Medical School , Boston, Massachusetts 02115, United States.
PMID: 28337328 DOI: 10.1021/acsmedchemlett.7b00008
Abstract

Here we report the structure-activity relationship (SAR) investigations of QL-XII-47 (QL47), a compound that possesses broad-spectrum Antiviral activity against Dengue Virus and Other RNA viruses. A medicinal chemistry campaign initiated from QL47, a previously reported covalent Btk Inhibitor, to derive YKL-04-085, which is devoid of any kinase activity when screened against a panel of 468 kinases and with improved pharmacokinetic properties. Both QL47 and YKL-04-085 are potent inhibitors of viral translation and exhibit cellular Antiviral activity at 35-fold lower concentrations relative to inhibition of host-cell proliferation.

Keywords
Dengue virus; QL47; broad-spectrum antiviral; structure−activity relationship.
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